The vitamin D receptor is a 50 kD protein which mediates the effects of vitamin D on gene regulation. Its structure remains unknown. We are particularly interested in the structure of the ligand-binding domain of the receptor, which is hypothesized to undergo a conformational change upon binding of 1,25-(OH)2D3 leading to transcriptional upregulation of vitamin D responsive genes. We have developed a method for producing this domain in large quantities in bacteria as a fusion protein with glutathione-S-transferase. Once purified, the ligand-binding domain can be cleaved from the N-terminal glutathoine-S-transferase to yield a 35 kD protein which retains wild-type affinity for ligand. We wish to carry out NMR studies of this domain in order to determine its solution structure. Initial studies will be done on non-isotopically labelled protein to ascertain if the domain is ameanable to NMR analysis. If these results appear promising, the fusion protein will be labelled with 13C and 15N and further analysis carried out to determine the structure both with and without bound ligand.